Three-dimensional perfused tumour spheroid model for anti-cancer drug screening

用于抗癌药物筛选的三维灌注肿瘤球体模型

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Abstract

OBJECTIVE: To build an in vitro-perfused, three-dimensional (3D) spheroid model based on the TissueFlex system for anti-cancer drug efficacy testing in order to mimic avascular micro-tissues with inherent O2, nutrient and metabolite gradients, and to provide a more accurate prediction of drug toxicity and efficacy than traditional in vitro tumour models in conventional static culture well plates. RESULTS: The perfused cancer spheroid model showed higher cell viability and increased diameter of spheroids over a relatively long culture period (17 days). Three anti-cancer drugs with different cytotoxic mechanisms were tested. In perfusion, lower cytotoxicity was observed for traditional cytotoxic drug 5-fluorouracil and microtubule-interfering, paclitaxel, showed greater interruption of spheroid integrity. For the hypoxic-dependent drug, tirapazamine, there was no significant difference observed between static and perfusion cultures. CONCLUSION: The perfusion culture provides a better homeostasis for cancer cell growth in a more controllable working platform for long-term drug testing.

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